Tetrahedron DNA nanostructure/iron-based nanomaterials for combined tumor therapy

Triple-negative breast cancer, due to its aggressive nature and lack of targeted treatment, faces serious challenges in breast cancer treatment. Conventional therapies, such as chemotherapy, are encumbered by a range of limitations, and there is an urgent need for more effective treatment strategies. Ferroptosis, as an iron-dependent form of cell death, has exhibited promising potential in cancer treatment. Combining ferroptosis with other cancer therapies offers new avenues for treatment. Tetrahedral DNA nanostructure (TDN), a novel DNA-based three-dimensional (3D) nanomaterial, is promising drug delivery vehicle and can be utilized for functionalizing inorganic nanomaterials. In this work, we have demonstrated the preparation of Fe3O4-PEI@TDN-DOX nanocomposites and elucidated their antitumor mechanism. The TDN facilitated the enhanced cellular uptake of polyetherimide (PEI)-modified Fe3O4, and the delivery of the chemotherapeutic drug doxorubicin (DOX) further augmented their anti-tumor effect. This novel strategy can destroy the tumor redox homeostasis and produce overwhelming lipid peroxides, consequently sensitizing the tumor to ferroptosis. The integration of ferroptosis with other cancer therapies opens up new possibilities for treatment. This research provides valuable mechanistic insights and practical strategies for leveraging nanotechnology to induce ferroptosis and amplify its impact on tumor cells.